基于化学模式识别和网络药理学的羊踯躅质量标志物预测分析  

Prediction Analysis of Quality Markers of Rhododendron molle G.Don Based on Chemical Pattern Recognition and Network Pharmacology

作　　者：梅文亚 于俊保 邓婷 刘湘丹[1,2,3] 童巧珍 王志辉[1,2] 刘笑蓉 周日宝[1,2,3] MEI Wenya;YU Junbao;DENG Ting;LIU Xiangdan;TONG Qiaozhen;WANG Zhihui;LIU Xiaorong;ZHOU Ribao(School of Pharmacy,Hunan University of Chinese Medicine,Changsha 410208,China;Key Research Laboratory of Germplasm Resources and Standardized Planting of Genuine Regional Medicinal Materials Produced in Hunan Province,Changsha 410208,China;Key Laboratory of Modern Research of Traditional Chinese Medicine,Education Department of Hunan Province,Changsha 410208,China)

机构地区：[1]湖南中医药大学药学院,长沙410208 [2]湘产大宗道地药材种质资源及规范化种植重点研究室,长沙410208 [3]湖南省普通高等学校中药现代化研究重点实验室,长沙410208

出　　处：《中国药学杂志》2024年第21期2030-2041,共12页Chinese Pharmaceutical Journal

基　　金：国家现代农业产业技术体系项目资助(CARS-21);湖南省中医药管理局重点项目资助(A2024002);湖南中医药大学校级科研项目重点项目资助(2023-27);湖南中医药大学科研创新项目资助(2023-102);湖南中医药大学重点学科中药学科项目资助(校行发规字[2023]2);湖南省教育厅优秀青年项目资助(23B0385);湖南省自然科学基金项目资助(2022JJ80086);湖南省卫生健康委计划研究项目资助(D202302078705);2020年湖南省一流本科专业建设点项目资助(湘教通[2020]248号);2020年国家级一流本科专业建设点项目资助(教高厅函[2021]7号)。

摘　　要：目的 基于高效液相色谱-蒸发光散射检测器(HPLC-ELSD)和网络药理学筛选羊踯躅质量标志物(quality markers, Q-marker),比较羊踯躅不同部位、不同花期、不同产地Q-marker含量,挖掘羊踯躅潜在药用价值并推测其可能的作用机制。方法 采用HPLC-ELSD建立羊踯躅指纹图谱,进行聚类分析(hierarchical cluster analysis, HCA)、主成分分析(principal component analysis, PCA)、正交偏最小二乘法判别分析(orthogonal partial least squares discriminant analysis, OPLS-DA),利用网络药理学方法构建“成分-靶点-通路-药理作用-功效”网络图,并进行疾病预测,筛选羊踯躅的Q-marker并进行定量分析。结果 本研究建立了11批羊踯躅药材的指纹图谱,共标定10个共有峰,经分析得到4个差异性成分,预测闹羊花毒素-Ⅲ、闹羊花毒素-Ⅱ、金丝桃苷、槲皮苷为羊踯躅的Q-marker候选成分并进行网络药理学分析,涉及84个靶点蛋白,包括ATK1、TNF、INS等,作用于159条信号通路,对肿瘤、自身免疫性疾病、心血管疾病等存在潜在治疗作用。成分含量测定结果显示羊踯躅以盛开期花入药可能具有更好的疗效,并以S10产地最优。结论 通过化学模式识别、指纹图谱及网络药理学预测了羊踯躅的Q-marker,证明羊踯躅可通过多靶点、多途径治疗疾病,为完善建立羊踯躅质量控制标准及其对疾病治疗机制的进一步探索提供参考。OBJECTIVE To screen the quality markers(Q-marker)of Rhododendron molle based on HPLC-ELSD and network pharmacology,compare the contents of quality markers in different parts,different flowering periods and different producing areas of R.molle,and explore the potential medicinal value of R.molle and speculate its possible mechanism of action.METHODS HPLC-ELSD was used to establish the fingerprint of R.molle,and hierarchical clustering analysis(HCA),principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA)were carried out.The network diagram of'component-target-pathway-pharmacological effect-efficacy'was constructed by network pharmacology method,and the disease prediction was carried out.The quality markers of R.molle were screened and quantitatively analyzed.RESULTS In this study,the fingerprints of 11 batches of Rhododendron molle were established,and total of 10 common peaks were calibrated.Four differential components were obtained after analysis.It was predicted that rhodojaponin-Ⅲ,rhodojaponin-Ⅱ,hyperoside and quercitrin were candidate components of quality markers of R.molle and network pharmacology analysis was performed.It involved 84 target proteins,including ATK1,TNF,INS,etc.,acting on 159 signaling pathways,and had potential therapeutic effects on tumors,autoimmune diseases,and cardiovascular diseases.The results of component content determination showed that the flowering of Rhododendron molle might have better curative effect,and the S10 origin was the best.CONCLUSION The quality markers of R.molle are predicted by chemical pattern recognition,fingerprint and network pharmacology.It is proved that R.molle could treat diseases through multiple targets and multiple pathways,which provides a reference for improving the establishment of quality control standards of R.molle and further exploring the mechanism of disease treatment.

关 键 词：羊踯躅 指纹图谱 质量标志物 化学模式识别 网络药理学 

分 类 号：R282[医药卫生—中药学]